Download Metabolism Fact Sheet - Barth Syndrome Foundation

METABOLISM OF BARTH SYNDROME
Metabolism Fact Sheet
Metabolism is the sum of all chemical processes that take place in our body. Some of these processes deal with
the need of the body for energy to drive its vital needs. This can be understood as a way in which cells burn food
to produce energy in a smart way without actually raising the temperature of the body. This is similar to a car’s
engine burning gasoline to produce the energy or torque that turns the drive train that spins the car’s wheels (the
energy we need to move and think). The major building blocks are carbohydrates, amino acids, and fats (lipids).
Every step of metabolism can be defined as converting substance A into substance B. Every conversion step
requires a specific protein, called an enzyme, to make the reaction happen in a precise way and without the need
for elevating body temperature.
Enzymes are proteins with a specific purpose to promote particular chemical processes in the body, such as
needed for growth, energy etc. Other proteins are part of the structure of our body comparable to building
blocks. All proteins made by our body are made of amino-acids. These are the building blocks of the proteins.
All proteins are made from such amino-acids. The order in which these amino-acids are arranged in the protein
determines their function. This order is “encoded” by genes, which contain the blueprint for each protein.
Mutations in a gene can cause a disturbed order of amino-acids in the protein, and the result is a malformed or
inactive protein. Some mutations totally eliminate the protein. The degree of the mutation determines the degree
to which the protein is functional (mild abnormality), or loses all of its function. In the case of Barth syndrome the
mutated gene is the Tafazzin or TAZ gene. The protein is tafazzin or TAZ protein. We believe that the task of
tafazzin is to modify cardiolipin which is a complet phospholipid, or fat, that is essential for normal energy
production. Summarizing: a gene named TAZ encodes a protein called tafazzin that probably functions as an
enzyme to help make mature cardiolipin.
Cardiolipin is made first with one kind of fatty acids attached to it which are mostly saturated, then the original
fatty acids are removed and other fatty acids are attached, which are mostly unsaturated. For cardiolipin to work
properly, it must have unsaturated fatty acids attached. The TAZ gene encodes a protein with an amino acid
sequence called acyltransferases. Acyl- means fatty acid or fat. Transferase does mean to transfer this fatty
acuid from one thing or molecule o another. Acyltransferases are enzymes that remodel phospholipids In Barth
syndrome, cells cannot add the unsaturated fatty acids to the premature form of cardiolipin. Therefore, in Barth
syndrome, the level of cardiolipin is reduced, and monolysocardiolipin (an intermediary product) accumulates.
We believe that taz is the enzyme involved in converting the premature cardiolipin to the mature form does not
work properly. It should be understood that tafazzin is the name of the protein while acyltransferase means the
function of the enzyme. As far as we know at this moment tafazzin is an acyltransferase. Acyltransferase literally
means: an enzyme that transfers lipid tails (acyl groups). There are many different acyltransferases in our body,
but only the acyltransferase involved in the synthesis of cardiolipin concerns us here. It is identical with tafazzin.
Cardiolipin is found only in particular regions of all living cells called mitochondria. Mitochondria are closed
compartments, which are well insulated or separated from the rest of the cell by having an outer and an inner
membrane. Their basic function is to produce energy in a form that can be carried to other parts of the cell to
drive all kinds of enzymatic reactions. The energy produced by the mitochondria is stored in the form of a
chemical called adenosine triphosphate, or ATP. When the breakdown products of the food that we eat enter the
mitochondria for processing, they're passed along a well-orchestrated assembly line made up of hundreds of
proteins, each with a specific role to play in the energy production process. Raw materials enter the beginning of
the assembly line, and ATP energy molecules come out the other side. As a result, mitochondria are essential to
the proper functioning of muscle cells, including those of heart and skeletal muscle. Mitochondria consist of a
smooth outer membrane and a twisted inner membrane that is arranged in multiple folds. Many individuals with
Barth syndrome have structural abnormalities of mitochondria, including mitochondria with unusually shaped
inner membranes that contain collections of abnormally stored materials.
Electron microscopic
photograph of a
normal mitochondrion.
Note the parallel array
of so called “cristae”
where energy
producing complexes
are attached.
Electron microscopic
photograph of
mitochondria in the
heart of a child with
Barth syndrome.
Notice the abnormal
course of cristae.
Metabolic Fact Sheet
The Barth Syndrome Foundation www.barthsyndrome.org
Oct. 11, 2005 PGB, AS
DISCLAIMER: This fact sheet is designed for educational purposes only and is not intended to serve as medical advice. The information
provided here should not be used for diagnosing or treating a health problem or disease. It is not a substitute for professional care.
Glossary of Terms
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Acidosis: Elevated amounts of organic acids in the blood, which accumulate when food is not properly
metabolized.
ADP: Adenosine diphosphate; the low energy product produced when ATP releases energy to the cell.
ATP: Adenosine triphosphate; cellular energy is stored in the third phosphate bond. ATP is formed from
ADP and phosphate in the process known as oxidative phosphorylation.
Beta-oxidation: A series of metabolic reactions necessary for burning fatty acids (fats).
Carbohydrates: An organic compound derived from carbon, hydrogen, and oxygen that is an important
source of food and energy for humans and animals. Sugar, starch, and cellulose are carbohydrates
Cardiolipin: An important component of the mitochondrial membrane typically present in metabolically
active cells of the heart and skeletal muscle. It has also been observed in certain bacterial membranes. It
serves as an insulator and stabilizes the activity of protein complexes important to the electron transport
chain.
Carnitine (beta-hydroxy-gamma-N-trimiethylamino-butyrate): Responsible for the transport of long chain
fatty acids into mitochondria. Carnitine is made from muscle protein
Complex I: NADH-Coenzyme Q oxidoreductase (part of the Electron Transport Chain).
Complex II: Succinate dehydrogenase (part of the Electron Transport Chain).
Complex III: Coenzyme Q-cytochrome c oxidoreductase (part of the Electron Transport Chain).
Complex IV: Cytochrome c oxidase (COX) (part of the Electron Transport Chain).
Complex X V: ATP synthase (part of the Electron Transport Chain).
Creatine: Allows the muscle to use ATP.
Enzyme: A protein that speeds up a chemical reaction or causes a chemical change in another substance.
Enzymes do their work without being changed or used up in the process.
Lactate or Lactic Acid: A chemical that is formed when sugars are broken down for energy without the
presence of adequate oxygen. Lactic acid cannot be used by the body and will accumulate in blood and
urine. Lactic acid causes the muscle pain when one runs too fast for too long. In people with mitochondrial
disorders, lactic acid forms when the oxidative capacity (ability to burn foods using oxidative
phosphorylation) of the person is impaired.
Lipids: Any of a group of organic compounds consisting of fats, oils, and related substances that, along
with proteins and carbohydrates, are the structural components of living cells.
Mitochondria: A part of the cell (organelle) that is responsible for energy production. The organelle consists
of two sets of membranes, a smooth continuous outer coat and an inner membrane arranged in tubules or in
folds that form plate-like double membranes (cristae); the principal energy source of the cell, containing the
cytochrome enzymes of terminal electron transport and the enzymes of the citric acid cycle, fatty acid
oxidation, and oxidative phosphorylation. Responsible for converting nutrients into energy as well as many
other specialized tasks.
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Metabolic Fact Sheet
The Barth Syndrome Foundation www.barthsyndrome.org
Oct. 11, 2005 PGB, AS
DISCLAIMER: This fact sheet is designed for educational purposes only and is not intended to serve as medical advice. The information
provided here should not be used for diagnosing or treating a health problem or disease. It is not a substitute for professional care.